JPH04330055A - Novel benzylidene cinnamic acid derivative - Google Patents
Novel benzylidene cinnamic acid derivativeInfo
- Publication number
- JPH04330055A JPH04330055A JP3142275A JP14227591A JPH04330055A JP H04330055 A JPH04330055 A JP H04330055A JP 3142275 A JP3142275 A JP 3142275A JP 14227591 A JP14227591 A JP 14227591A JP H04330055 A JPH04330055 A JP H04330055A
- Authority
- JP
- Japan
- Prior art keywords
- benzylidene
- formula
- cis
- isoindolinylcarbonyl
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- -1 benzylidene cinnamic acid derivative Chemical class 0.000 title abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims abstract description 12
- 235000019260 propionic acid Nutrition 0.000 claims abstract description 6
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 3
- KYILORDWJFEQBS-UHFFFAOYSA-N 2-benzylidenebutanedioic acid Chemical class OC(=O)CC(C(O)=O)=CC1=CC=CC=C1 KYILORDWJFEQBS-UHFFFAOYSA-N 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- ZXVXJGMFEGAQEI-CLTATDAWSA-N (2e)-4-[(3ar,7as)-1,3,3a,4,5,6,7,7a-octahydroisoindol-2-yl]-2-benzylidene-4-oxobutanoic acid Chemical compound C([C@@H]1CCCC[C@@H]1C1)N1C(=O)C/C(C(=O)O)=C\C1=CC=CC=C1 ZXVXJGMFEGAQEI-CLTATDAWSA-N 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 125000002619 bicyclic group Chemical group 0.000 claims description 3
- 229910052799 carbon Chemical group 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 abstract description 22
- 239000008280 blood Substances 0.000 abstract description 5
- 210000004369 blood Anatomy 0.000 abstract description 5
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 abstract 2
- 102000004877 Insulin Human genes 0.000 abstract 1
- 108090001061 Insulin Proteins 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- FXEDRSGUZBCDMO-UHFFFAOYSA-N cinnamic acid anhydride Natural products C=1C=CC=CC=1C=CC(=O)OC(=O)C=CC1=CC=CC=C1 FXEDRSGUZBCDMO-UHFFFAOYSA-N 0.000 abstract 1
- 230000001747 exhibiting effect Effects 0.000 abstract 1
- 229940125396 insulin Drugs 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 8
- ODSNARDHJFFSRH-OCAPTIKFSA-N (3as,7ar)-2,3,3a,4,5,6,7,7a-octahydro-1h-isoindole Chemical compound C1CCC[C@@H]2CNC[C@@H]21 ODSNARDHJFFSRH-OCAPTIKFSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- FHUNJZMVODDGDH-CLTATDAWSA-N (2e)-4-[(3ar,7as)-1,3,3a,4,7,7a-hexahydroisoindol-2-yl]-2-benzylidene-4-oxobutanoic acid Chemical compound C([C@@H]1CC=CC[C@@H]1C1)N1C(=O)C/C(C(=O)O)=C\C1=CC=CC=C1 FHUNJZMVODDGDH-CLTATDAWSA-N 0.000 description 2
- WHRPHGQMEZWMNF-UHFFFAOYSA-N 3-benzylideneoxolane-2,5-dione Chemical compound O=C1OC(=O)CC1=CC1=CC=CC=C1 WHRPHGQMEZWMNF-UHFFFAOYSA-N 0.000 description 2
- ZXVXJGMFEGAQEI-IYBDPMFKSA-N 4-[(3as,7ar)-1,3,3a,4,5,6,7,7a-octahydroisoindol-2-yl]-2-benzylidene-4-oxobutanoic acid Chemical compound C([C@@H]1CCCC[C@@H]1C1)N1C(=O)CC(C(=O)O)=CC1=CC=CC=C1 ZXVXJGMFEGAQEI-IYBDPMFKSA-N 0.000 description 2
- NZQOHWNCUBISTI-HEEIEUBCSA-N C([C@H]1[C@H](CCCC1)C1)N1C(=O)C\C(=C/c1ccccc1)C(=O)OCc1ccccc1 Chemical compound C([C@H]1[C@H](CCCC1)C1)N1C(=O)C\C(=C/c1ccccc1)C(=O)OCc1ccccc1 NZQOHWNCUBISTI-HEEIEUBCSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000002218 hypoglycaemic effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- HYBVBPUMYMIMGW-JXELUCIISA-N (2e)-4-[(4as,8ar)-3,4,4a,5,6,7,8,8a-octahydro-1h-isoquinolin-2-yl]-2-benzylidene-4-oxobutanoic acid Chemical compound C([C@@H]1CCCC[C@H]1CC1)N1C(=O)C/C(C(=O)O)=C\C1=CC=CC=C1 HYBVBPUMYMIMGW-JXELUCIISA-N 0.000 description 1
- ZXVXJGMFEGAQEI-LJXBNOSUSA-N (2z)-4-[(3as,7ar)-1,3,3a,4,5,6,7,7a-octahydroisoindol-2-yl]-2-benzylidene-4-oxobutanoic acid Chemical compound C([C@@H]1CCCC[C@@H]1C1)N1C(=O)C/C(C(=O)O)=C/C1=CC=CC=C1 ZXVXJGMFEGAQEI-LJXBNOSUSA-N 0.000 description 1
- ODSNARDHJFFSRH-YUMQZZPRSA-N (3ar,7ar)-2,3,3a,4,5,6,7,7a-octahydro-1h-isoindole Chemical compound C1CCC[C@H]2CNC[C@@H]21 ODSNARDHJFFSRH-YUMQZZPRSA-N 0.000 description 1
- PDELQDSYLBLPQO-JGVFFNPUSA-N (3as,7ar)-2,3,3a,4,5,6,7,7a-octahydro-1h-indole Chemical compound C1CCC[C@H]2NCC[C@@H]21 PDELQDSYLBLPQO-JGVFFNPUSA-N 0.000 description 1
- WHRPHGQMEZWMNF-RMKNXTFCSA-N (3e)-3-benzylideneoxolane-2,5-dione Chemical compound O=C1OC(=O)C\C1=C/C1=CC=CC=C1 WHRPHGQMEZWMNF-RMKNXTFCSA-N 0.000 description 1
- WHRPHGQMEZWMNF-TWGQIWQCSA-N (3z)-3-benzylideneoxolane-2,5-dione Chemical compound O=C1OC(=O)C\C1=C\C1=CC=CC=C1 WHRPHGQMEZWMNF-TWGQIWQCSA-N 0.000 description 1
- NENLYAQPNATJSU-IUCAKERBSA-N (4as,8ar)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline Chemical compound C1NCC[C@@H]2CCCC[C@H]21 NENLYAQPNATJSU-IUCAKERBSA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 1
- ARVHJVUVHJCQCY-QCADSSPNSA-N C(/C1=CC=CC=C1)=C(C(=O)O)/CC(=O)N1CC[C@@H]2CCCC[C@@H]12 Chemical compound C(/C1=CC=CC=C1)=C(C(=O)O)/CC(=O)N1CC[C@@H]2CCCC[C@@H]12 ARVHJVUVHJCQCY-QCADSSPNSA-N 0.000 description 1
- ZXVXJGMFEGAQEI-GSEUPMHVSA-N C(/C1=CC=CC=C1)=C(C(=O)O)/CC(=O)N1C[C@@H]2CCCC[C@H]2C1 Chemical compound C(/C1=CC=CC=C1)=C(C(=O)O)/CC(=O)N1C[C@@H]2CCCC[C@H]2C1 ZXVXJGMFEGAQEI-GSEUPMHVSA-N 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229940122199 Insulin secretagogue Drugs 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- QQIFKFNDHCSBJH-SSHXDOOXSA-N methyl (2e)-4-[(3as,7ar)-1,3,3a,4,5,6,7,7a-octahydroisoindol-2-yl]-2-benzylidene-4-oxobutanoate Chemical compound C([C@@H]1CCCC[C@@H]1C1)N1C(=O)C/C(C(=O)OC)=C\C1=CC=CC=C1 QQIFKFNDHCSBJH-SSHXDOOXSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000002461 renin inhibitor Substances 0.000 description 1
- 229940086526 renin-inhibitors Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000000580 secretagogue effect Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- ADEUVSZQTAXWJV-BKXHHDMDSA-M sodium;(2e)-4-[(3ar,7as)-1,3,3a,4,5,6,7,7a-octahydroisoindol-2-yl]-2-benzylidene-4-oxobutanoate Chemical compound [Na+].C([C@@H]1CCCC[C@@H]1C1)N1C(=O)C/C(C(=O)[O-])=C\C1=CC=CC=C1 ADEUVSZQTAXWJV-BKXHHDMDSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
Abstract
Description
【０００１】0001
【産業上の利用分野】本発明は医薬品として有用な新規
なベンジリデンコハク酸誘導体およびその塩に関するも
のである。TECHNICAL FIELD The present invention relates to novel benzylidene succinic acid derivatives and salts thereof useful as pharmaceuticals.
【０００２】さらに詳しく述べれば、本発明は血糖低下
作用を有し、糖尿病治療剤として有用な、一般式More specifically, the present invention provides compounds of the general formula
【００
０３】00
03]
【化６】
（式中のＡは環内に１〜２個の不飽和結合を有すること
もある二環性縮環状アミノ基であり、Ｒは水素原子また
は炭素数１〜６の低級アルキル基または炭素数７〜１０
のアラルキル基である）で表される新規なベンジリデン
コハク酸誘導体およびその塩に関するものである。[Chemical formula 6] (In the formula, A is a bicyclic condensed amino group that may have 1 to 2 unsaturated bonds in the ring, and R is a hydrogen atom or a lower alkyl group having 1 to 6 carbon atoms. Or carbon number 7-10
The present invention relates to novel benzylidene succinic acid derivatives and salts thereof, represented by the following aralkyl group:
【０００４】0004
【従来の技術】本発明のようなベンジリデンコハク酸誘
導体に関し、一般式[Prior Art] Regarding the benzylidene succinic acid derivatives of the present invention, the general formula
【０００５】[0005]
【化７】
（式中のＲ１は水素原子またはメチル基である）で表さ
れる化合物がレニン阻害剤の製造中間体として用いられ
ているが、それ自体の薬理作用等については全く報告さ
れていない。〔ジャーナル オブ メディシナル
ケミストリー（Ｊ．Ｍｅｄ．Ｃｈｅｍ．）３１巻、２
２７７〜２２８８ページ、１９８８年〕The compound represented by [Chemical formula 7] (wherein R1 is a hydrogen atom or a methyl group) is used as an intermediate in the production of renin inhibitors, but there have been no reports on its pharmacological effects etc. do not have. [Journal of Medicinal
Chemistry (J.Med.Chem.) Volume 31, 2
pages 277-2288, 1988]
【０００６】[0006]
【発明が解決しようとする課題】本発明の目的は血糖低
下作用を示し、糖尿病治療剤として有用な新規なベンジ
リデンコハク酸誘導体を提供することである。OBJECTS OF THE INVENTION An object of the present invention is to provide a novel benzylidene succinic acid derivative that exhibits a hypoglycemic effect and is useful as a therapeutic agent for diabetes.
【０００７】[0007]
【課題を解決するための手段】本発明者らは鋭意研究を
重ねた結果、前記一般式（Ｉ）で表されるベンジリデン
コハク酸誘導体およびその塩が、インスリン分泌促進作
用を有し、好適な血糖低下作用を示すことを見出し、本
発明を成すに至った。[Means for Solving the Problems] As a result of intensive research, the present inventors have found that the benzylidene succinic acid derivative represented by the general formula (I) and its salt have an insulin secretagogue effect and are suitable for It was discovered that it exhibits a blood sugar-lowering effect, and the present invention was completed.
【０００８】本発明の前記一般式（Ｉ）の化合物におい
て、環内に１〜２個の不飽和結合を有することもある環
状アミノ基とは、１〜２個の不飽和結合を有することも
ある５〜６員環の環状炭化水素基と５〜６員環の環状ア
ミノ基が縮合した二環性の縮環状アミノ基を意味し、例
えば、シス−ヘキサヒドロ−１−インドリニル、トラン
ス−ヘキサヒドロ−１−インドリニル、４，５，６，７
−テトラヒドロ−２−イソインドリニル、トランス−３
ａ，４，７，７ａ−テトラヒドロ−２−イソインドリニ
ル、シス−３ａ，４，７，７ａ−テトラヒドロ−２−イ
ソインドリニル、３ａ，４，５，７ａ−テトラヒドロ−
２−イソインドリニル、３ａ，７ａ−ジヒドロ−２−イ
ソインドリニル、トランス−ヘキサヒドロ−１−インド
リニル、シス−ヘキサヒドロ−１−インドリニル、トラ
ンス−３ａ，４，７，７ａ−テトラヒドロ−１−インド
リニル、シス−３ａ，４，７，７ａ−テトラヒドロ−１
−インドリニル、３ａ，６，７，７ａ−テトラヒドロ−
１−インドリニル、３ａ，７ａ−ジヒドロ−１−インド
リニル、シス−オクタヒドロ−２−ピリイソジン−２−
イル、トランス−オクタヒドロ−２−ピリイソジン−２
−イル、シス−オクタヒドロ−１−ピリイソジン−１−
イル、トランス−オクタヒドロ−１−ピリイソジン−１
−イル、シス−２−アザビシクロ〔３．３．０〕オクタ
ン−２−イル、トランス−２−アザビシクロ〔３．３．
０〕オクタン−２−イル、シス−３−アザビシクロ〔３
．３．０〕オクタン−３−イル、１，２，３，４，５，
６，７，８−オクタヒドロ−２−イソキノリル、シス−
１，２，３，４，４ａ，５，８，８ａ−オクタヒドロ−
２−イソキノリル、トランス−１，２，３，４，４ａ，
５，８，８ａ−オクタヒドロ−２−イソキノリル、トラ
ンス−１，２，３，４，４ａ，７，８，８ａ−オクタヒ
ドロ−２−イソキノリル、トランス−１，２，３，４，
４ａ，５，６，８ａ−オクタヒドロ−２−イソキノリル
、シス−デカヒドロ−２−イソキノリル、トランス−デ
カヒドロ−２−イソキノリル、１，２，３，４，５，８
−ヘキサヒドロ−２−イソキノリル、トランス−デカヒ
ドロ−１−キノリル、シス−デカヒドロ−１−キノリル
、シス−１，２，３，４，４ａ，５，６，８ａ−オクタ
ヒドロ−１−キノリル、１，２，３，４，５，６，７，
８−オクタヒドロ−１−キノリルなどをあげることがで
きる。In the compound of the general formula (I) of the present invention, the cyclic amino group which may have 1 to 2 unsaturated bonds in the ring refers to a cyclic amino group which may have 1 to 2 unsaturated bonds within the ring. It refers to a bicyclic condensed amino group in which a certain 5- to 6-membered cyclic hydrocarbon group and a 5- to 6-membered cyclic amino group are condensed, such as cis-hexahydro-1-indolinyl, trans-hexahydro- 1-indolinyl, 4,5,6,7
-tetrahydro-2-isoindolinyl, trans-3
a,4,7,7a-tetrahydro-2-isoindolinyl, cis-3a,4,7,7a-tetrahydro-2-isoindolinyl, 3a,4,5,7a-tetrahydro-
2-isoindolinyl, 3a,7a-dihydro-2-isoindolinyl, trans-hexahydro-1-indolinyl, cis-hexahydro-1-indolinyl, trans-3a,4,7,7a-tetrahydro-1-indolinyl, cis-3a, 4,7,7a-tetrahydro-1
-indolinyl, 3a,6,7,7a-tetrahydro-
1-indolinyl, 3a,7a-dihydro-1-indolinyl, cis-octahydro-2-pyriisodine-2-
yl, trans-octahydro-2-pyriisodine-2
-yl, cis-octahydro-1-pyriisodine-1-
yl, trans-octahydro-1-pyriisodine-1
-yl, cis-2-azabicyclo[3.3.0]octan-2-yl, trans-2-azabicyclo[3.3.
0] Octane-2-yl, cis-3-azabicyclo[3
．． 3.0] Octane-3-yl, 1,2,3,4,5,
6,7,8-octahydro-2-isoquinolyl, cis-
1,2,3,4,4a,5,8,8a-octahydro-
2-isoquinolyl, trans-1,2,3,4,4a,
5,8,8a-octahydro-2-isoquinolyl, trans-1,2,3,4,4a,7,8,8a-octahydro-2-isoquinolyl, trans-1,2,3,4,
4a,5,6,8a-octahydro-2-isoquinolyl, cis-decahydro-2-isoquinolyl, trans-decahydro-2-isoquinolyl, 1,2,3,4,5,8
-hexahydro-2-isoquinolyl, trans-decahydro-1-quinolyl, cis-decahydro-1-quinolyl, cis-1,2,3,4,4a,5,6,8a-octahydro-1-quinolyl, 1,2 ,3,4,5,6,7,
Examples include 8-octahydro-1-quinolyl.
【０００９】本発明の一般式（Ｉ）で表されるベンジリ
デンコハク酸誘導体は新規な化合物であり、以下のよう
にして製造することができる。The benzylidene succinic acid derivative represented by the general formula (I) of the present invention is a new compound and can be produced as follows.
【００１０】すなわち、式[0010] That is, the formula
【化８】 で表されるベンジリデンコハク酸無水物と、一般式[Chemical formula 8] Benzylidene succinic anhydride represented by and the general formula
【０
０１１】
Ａ − Ｈ
（ＩＩＩ）（式中のＡは前記と同じ意味をも
つ）で表される化合物とを反応させ、必要に応じエステ
ル化することにより製造することができる。0
011 A-H
It can be produced by reacting the compound represented by (III) (in which A has the same meaning as above) and esterifying if necessary.
【００１２】本製造方法で出発物質として用いられる式
（ＩＩ）のベンジリデンコハク酸無水物は公知の化合物
であり、文献記載の方法により容易に製造することがで
きる。The benzylidene succinic anhydride of formula (II) used as a starting material in this production method is a known compound and can be easily produced by methods described in literature.
【００１３】また、一般式（ＩＩＩ）で表されるアミン
類も公知化合物であり、市販品として購入するかあるい
は、文献記載の方法により容易に製造することができる
。The amines represented by the general formula (III) are also known compounds, and can be purchased as commercial products or easily produced by methods described in literature.
【００１４】本発明の前記一般式（Ｉ）の化合物はマウ
スを用いたｉｎ ｖｉｖｏ の血糖低下試験におい
て０．１〜１０ｍｇ／ｋｇ程度の経口投与により明らか
な血糖低下作用を示す。The compound of general formula (I) of the present invention exhibits a clear blood sugar lowering effect when administered orally at a dose of about 0.1 to 10 mg/kg in an in vivo blood sugar lowering test using mice.
【００１５】本発明の前記一般式（Ｉ）の化合物は二重
結合によるＥ体およびＺ体の幾何異性体が存在し、本発
明においてはそのいずれをも含まれるが、インスリン分
泌促進作用および血糖低下作用のいずれにおいてもＥ体
が好適な薬理作用を発揮する。The compound of the general formula (I) of the present invention has geometric isomers of E form and Z form due to double bonds, and the present invention includes both of them. In both of the lowering effects, the E form exhibits a suitable pharmacological effect.
【００１６】また、本発明の前記一般式（Ｉ）の化合物
でＲが水素原子である化合物は常法に従い、薬理学的に
許容される塩とすることができる。このようなものとし
て、例えば、ナトリウム塩、カルシウム塩などのような
無機塩基との塩、モルホリン、ピペリジンなどの有機ア
ミン、あるいはアミノ酸との塩などをあげることができ
る。これらの薬理学的に許容される塩もカルボン酸と同
様にインスリン分泌促進作用と血糖低下作用を示し、糖
尿病治療剤として有用である。Further, the compound of the general formula (I) of the present invention in which R is a hydrogen atom can be converted into a pharmacologically acceptable salt according to a conventional method. Examples of such substances include salts with inorganic bases such as sodium salts and calcium salts, salts with organic amines such as morpholine and piperidine, or salts with amino acids. Similar to carboxylic acids, these pharmacologically acceptable salts exhibit insulin secretion promoting and hypoglycemic effects, and are useful as antidiabetic agents.
【００１７】本発明の一般式（Ｉ）で表されるベンジリ
デンコハク酸誘導体およびその塩を実際の治療に用いる
場合、適当な医薬品組成物、例えば錠剤、散剤、顆粒剤
、カプセル剤、注射剤などとして経口的あるいは非経口
的に投与される。これらの医薬品組成物は一般の調剤に
おいて行われる製剤学的手法により調製することができ
る。When the benzylidene succinic acid derivative represented by general formula (I) and its salt of the present invention are used in actual treatment, suitable pharmaceutical compositions such as tablets, powders, granules, capsules, injections, etc. It is administered orally or parenterally. These pharmaceutical compositions can be prepared by pharmaceutical techniques commonly used in pharmaceutical preparations.
【００１８】投与量は対象となる患者の性別、年齢、体
重、症状の度合などによって適宜決定されるが、経口投
与の場合、概ね成人１日当たり１０〜１０００ｍｇ、非
経口投与の場合、概ね成人１日当たり１〜１００ｍｇの
範囲内で投与される。The dosage is appropriately determined depending on the sex, age, weight, severity of symptoms, etc. of the target patient, but in the case of oral administration, it is approximately 10 to 1000 mg per day for an adult, and in the case of parenteral administration, it is approximately 100 mg per day for an adult. It is administered in the range of 1-100 mg per day.
【００１９】[0019]
【実施例】本発明の内容を以下の実施例でさらに詳細に
説明する。なお、各実施例中の化合物の融点はすべて未
補正である。EXAMPLES The contents of the present invention will be explained in more detail in the following examples. Note that all melting points of compounds in each example are uncorrected.
【００２０】実施例 １
（Ｅ）−２−ベンジリデン−３−（シス−ヘキサヒドロ
−２−イソインドリニルカルボニル）プロピオン酸Example 1 (E)-2-Benzylidene-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionic acid
【０
０２１】（Ｅ）−ベンジリデンコハク酸無水物１３．９
ｇの塩化メチレン１２０ｍｌ懸濁液に、シス−ヘキサヒ
ドロイソインドリン１２．０ｇを滴下し、室温で２時間
撹拌した。反応液を１規定塩酸および飽和食塩水で順次
洗浄し、無水硫酸マグネシウムで乾燥した。溶媒を減圧
下に留去し、酢酸エチルより結晶化させ、（Ｅ）−２−
ベンジリデン−３−（シス−ヘキサヒドロ−２−イソイ
ンドリニルカルボニル）プロピオン酸１９．５ｇを得た
。0
(E)-Benzylidene succinic anhydride 13.9
12.0 g of cis-hexahydroisoindoline was added dropwise to 120 ml of methylene chloride suspension, and the mixture was stirred at room temperature for 2 hours. The reaction solution was washed successively with 1N hydrochloric acid and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and crystallized from ethyl acetate to give (E)-2-
19.5 g of benzylidene-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionic acid was obtained.
【００２２】[0022]
【００２３】実施例 ２
シス−ヘキサヒドロイソインドリンの代わりにシス−３
ａ，４，７，７ａ−テトラヒドロイソインドリンを用い
、実施例１と同様な方法で、下記の化合物を製造した。Example 2 Cis-3 instead of cis-hexahydroisoindoline
The following compound was produced in the same manner as in Example 1 using a,4,7,7a-tetrahydroisoindoline.
【００２４】（Ｅ）−２−ベンジリデン−３−（シス−
３ａ，４，７，７ａ−テトラヒドロ−２−イソインドリ
ニルカルボニル）プロピオン酸(E)-2-Benzylidene-3-(cis-
3a,4,7,7a-tetrahydro-2-isoindolinylcarbonyl)propionic acid
【００２５】[0025]
【００２６】実施例 ３
シス−ヘキサヒドロイソインドリンの代わりにトランス
−デカヒドロイソキノリンを用い、実施例１と同様な方
法で、下記の化合物を製造した。Example 3 The following compound was produced in the same manner as in Example 1, using trans-decahydroisoquinoline in place of cis-hexahydroisoindoline.
【００２７】（Ｅ）−２−ベンジリデン−３−（トラン
ス−デカヒドロ−２−イソキノリルカルボニル）プロピ
オン酸(E)-2-Benzylidene-3-(trans-decahydro-2-isoquinolylcarbonyl)propionic acid
【００２８】[0028]
【００２９】実施例 ４
シス−ヘキサヒドロイソインドリンの代わりにトランス
−ヘキサヒドロインドリンを用い、実施例１と同様な方
法で、下記の化合物を製造した。Example 4 The following compound was produced in the same manner as in Example 1, using trans-hexahydroindoline instead of cis-hexahydroisoindoline.
【００３０】（Ｅ）−２−ベンジリデン−３−（トラン
ス−ヘキサヒドロ−１−インドリニルカルボニル）プロ
ピオン酸(E)-2-Benzylidene-3-(trans-hexahydro-1-indolinylcarbonyl)propionic acid
【００３１】[0031]
【００３２】実施例 ５
シス−ヘキサヒドロイソインドリンの代わりにトランス
−ヘキサヒドロイソインドリンを用い、実施例１と同様
な方法で、下記の化合物を製造した。Example 5 The following compound was produced in the same manner as in Example 1, using trans-hexahydroisoindoline instead of cis-hexahydroisoindoline.
【００３３】（Ｅ）−２−ベンジリデン−３−（トラン
ス−ヘキサヒドロ−２−イソインドリニルカルボニル）
プロピオン酸(E)-2-Benzylidene-3-(trans-hexahydro-2-isoindolinylcarbonyl)
propionic acid
【００３４】[0034]
【００３５】実施例 ６
（Ｅ）−２−ベンジリデン−３−（シス−ヘキサヒドロ
−２−イソインドリニルカルボニル）プロピオン酸ナト
リウムExample 6 Sodium (E)-2-benzylidene-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionate
【００３６】（Ｅ）−２−ベンジリデン−３−（シス−
ヘキサヒドロ−２−イソインドリニルカルボニル）プロ
ピオン酸３１ｍｇのエタノール０．３ｍｌ溶液に１規定
水酸化ナトリウム０．１ｍｌを加え、室温で２時間撹拌
した。溶媒を減圧下に留去し、無色アモルファスの（Ｅ
）−２−ベンジリデン−３−（シス−ヘキサヒドロ−２
−イソインドリニルカルボニル）プロピオン酸ナトリウ
ム３０ｍｇを得た。(E)-2-Benzylidene-3-(cis-
To a solution of 31 mg of hexahydro-2-isoindolinylcarbonyl)propionic acid in 0.3 ml of ethanol was added 0.1 ml of 1N sodium hydroxide, and the mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure to obtain colorless amorphous (E
)-2-Benzylidene-3-(cis-hexahydro-2
30 mg of sodium -isoindolinylcarbonyl)propionate was obtained.
【００３７】[0037]
【００３８】実施例 ７
（Ｅ）−２−ベンジリデン−３−（シス−ヘキサヒドロ
−２−イソインドリニルカルボニル）プロピオン酸の代
わりに（Ｅ）−２−ベンジリデン−３−（シス−３ａ，
４，７，７ａ−テトラヒドロ−２−イソインドリニルカ
ルボニル）プロピオン酸を用い、実施例６と同様な方法
で、下記の化合物を製造した。Example 7 (E)-2-benzylidene-3-(cis-3a,
The following compound was produced in the same manner as in Example 6 using 4,7,7a-tetrahydro-2-isoindolinylcarbonyl)propionic acid.
【００３９】（Ｅ）−２−ベンジリデン−３−（シス−
３ａ，４，７，７ａ−テトラヒドロ−２−イソインドリ
ニルカルボニル）プロピオン酸ナトリウム(E)-2-Benzylidene-3-(cis-
Sodium 3a,4,7,7a-tetrahydro-2-isoindolinylcarbonyl)propionate
【００４０】
無色アモルファス[0040]
colorless amorphous
【００４１】実施例 ８
（Ｅ）−２−ベンジリデン−３−（シス−ヘキサヒドロ
−２−イソインドリニルカルボニル）プロピオン酸メチ
ルExample 8 Methyl (E)-2-benzylidene-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionate
【００４２】（Ｅ）−２−ベンジリデン−３−（シス−
ヘキサヒドロ−２−イソインドリニルカルボニル）プロ
ピオン酸５０ｍｇのエーテル溶液に撹拌下ジアゾメタン
のエーテル溶液を加え、室温で２時間撹拌した。溶媒を
減圧下に留去し、無色粘性油状の（Ｅ）−２−ベンジリ
デン−３−（シス−ヘキサヒドロ−２−イソインドリニ
ルカルボニル）プロピオン酸メチル５２ｍｇを得た。(E)-2-Benzylidene-3-(cis-
An ether solution of diazomethane was added to an ether solution of 50 mg of hexahydro-2-isoindolinylcarbonyl)propionic acid with stirring, and the mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure to obtain 52 mg of methyl (E)-2-benzylidene-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionate as a colorless viscous oil.
【００４３】[0043]
【００４４】実施例 ９
（Ｅ）−２−ベンジリデン−３−（シス−ヘキサヒドロ
−２−イソインドリニルカルボニル）プロピオン酸の代
わりに、（Ｅ）−２−ベンジリデン−３−（シス−３ａ
，４，７，７ａ−テトラヒドロ−２−イソインドリニル
カルボニル）プロピオン酸を用い実施例８と同様な方法
で、下記の化合物を製造した。Example 9 Instead of (E)-2-benzylidene-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionic acid, (E)-2-benzylidene-3-(cis-3a
, 4,7,7a-tetrahydro-2-isoindolinylcarbonyl)propionic acid in the same manner as in Example 8 to produce the following compound.
【００４５】（Ｅ）−２−ベンジリデン−３−（シス−
３ａ，４，７，７ａ−テトラヒドロ−２−イソインドリ
ニルカルボニル）プロピオン酸メチル(E)-2-Benzylidene-3-(cis-
Methyl 3a,4,7,7a-tetrahydro-2-isoindolinylcarbonyl)propionate
【００４６】[0046]
【００４７】実施例 １０
（Ｅ）−２−ベンジリデン−３−（シス−ヘキサヒドロ
−２−イソインドリニルカルボニル）プロピオン酸ベン
ジルExample 10 Benzyl (E)-2-benzylidene-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionate
【００４８】（Ｅ）−２−ベンジリデン−３−（シス−
ヘキサヒドロ−２−イソインドリニルカルボニル）プロ
ピオン酸５０ｍｇの塩化メチレン１ｍｌ溶液に撹拌下ト
リエチルアミン２３μｌおよびベンジルブロミド１９μ
ｌを加え、室温で１６時間撹拌した。反応液に塩化メチ
レンを加え、１規定塩酸、飽和炭酸水素ナトリウム水溶
液および飽和食塩水で順次洗浄し、無水硫酸マグネシウ
ムで乾燥した。溶媒を減圧下に留去し、無色粘性油状の
（Ｅ）−２−ベンジリデン−３−（シス−ヘキサヒドロ
−２−イソインドリニルカルボニル）プロピオン酸ベン
ジル５１ｍｇを得た。(E)-2-Benzylidene-3-(cis-
Add 23 μl of triethylamine and 19 μl of benzyl bromide to a solution of 50 mg of hexahydro-2-isoindolinylcarbonyl)propionic acid in 1 ml of methylene chloride with stirring.
1 was added and stirred at room temperature for 16 hours. Methylene chloride was added to the reaction solution, which was washed successively with 1N hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 51 mg of benzyl (E)-2-benzylidene-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionate as a colorless viscous oil.
【００４９】[0049]
【００５０】実施例 １１
ベンジルブロミドの代わりに、プロピルブロミドを用い
、実施例１０と同様な方法で、下記の化合物を製造した
。Example 11 The following compound was produced in the same manner as in Example 10 using propyl bromide instead of benzyl bromide.
【００５１】（Ｅ）−２−ベンジリデン−３−（シス−
ヘキサヒドロ−２−イソインドリニルカルボニル）プロ
ピオン酸プロピル(E)-2-Benzylidene-3-(cis-
Propyl hexahydro-2-isoindolinylcarbonyl)propionate
【００５２】[0052]
【００５３】実施例 １２
（Ｚ）−２−ベンジリデン−３−（シス−ヘキサヒドロ
−２−イソインドリニルカルボニル）プロピオン酸Example 12 (Z)-2-Benzylidene-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionic acid
【０
０５４】（Ｚ）−ベンジリデンコハク酸無水物１３９ｍ
ｇの塩化メチレン３０ｍｌ懸濁液にシス−ヘキサヒドロ
イソインドリン１２０ｍｇを滴下し、室温で２時間撹拌
した。反応液に２規定水酸化ナトリウムを加え、中性部
をエーテルで抽出除去したのち、水層を１規定塩酸で酸
性とし塩化メチレンで抽出した。有機層を飽和食塩水で
洗浄し、無水硫酸マグネシウムで乾燥した。溶媒を減圧
下に留去し、酢酸エチルより結晶化させ、（Ｚ）−２−
ベンジリデン−３−（シス−ヘキサヒドロ−２−イソイ
ンドリニルカルボニル）プロピオン酸１９０ｍｇを得た
。0
054 (Z)-Benzylidene succinic anhydride 139m
120 mg of cis-hexahydroisoindoline was added dropwise to a 30 ml suspension of methylene chloride of g, and the mixture was stirred at room temperature for 2 hours. After adding 2N sodium hydroxide to the reaction solution and removing the neutral part by extraction with ether, the aqueous layer was made acidic with 1N hydrochloric acid and extracted with methylene chloride. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and crystallized from ethyl acetate to give (Z)-2-
190 mg of benzylidene-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionic acid was obtained.
【００５５】[0055]
Claims (5)
もある二環性縮環状アミノ基であり、Ｒは水素原子また
は炭素数１〜６の低級アルキル基または炭素数７〜１０
のアラルキル基である）で表されるベンジリデンコハク
酸誘導体およびその塩。Claim 1: General formula [Formula 1] (In the formula, A is a bicyclic condensed amino group that may have 1 to 2 unsaturated bonds in the ring, and R is a hydrogen atom or a carbon number 1-6 lower alkyl group or carbon number 7-10
benzylidene succinic acid derivatives and salts thereof, which are an aralkyl group of
る請求項１記載のベンジリデンコハク酸誘導体およびそ
の塩。2. The benzylidene succinic acid derivative and its salt according to claim 1, represented by the general formula: [Image Omitted] (A and R in the formula have the same meanings as above).
２記載のベンジリデンコハク酸誘導体およびその塩。3. The benzylidene succinic acid derivative and its salt according to claim 2, represented by the general formula: [Image Omitted] (A in the formula has the same meaning as above).
ａ，４，７，７ａ−テトラヒドロ−２−イソインドリニ
ルカルボニル）プロピオン酸およびその塩。Claim 4: (E)-2-benzylidene-3-(cis-3
a,4,7,7a-tetrahydro-2-isoindolinylcarbonyl)propionic acid and its salts.
キサヒドロ−２−イソインドリニルカルボニル）プロピ
オン酸およびその塩。5. (E)-2-Benzylidene-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionic acid represented by the formula: [Image Omitted] and a salt thereof.
Priority Applications (13)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3142275A JP2686861B2 (en) | 1991-03-30 | 1991-03-30 | Novel benzylidene succinic acid derivative |
| AU12809/92A AU654331B2 (en) | 1991-03-30 | 1992-03-11 | Succinic acid compounds |
| CA002062877A CA2062877C (en) | 1991-03-30 | 1992-03-12 | Succinic acid compounds |
| DK041592A DK170973B1 (en) | 1991-03-30 | 1992-03-27 | Succinic compounds and pharmaceutical preparations containing them |
| NO921200A NO178371C (en) | 1991-03-30 | 1992-03-27 | succinic acid |
| FI921392A FI102172B (en) | 1991-03-30 | 1992-03-30 | Process for the preparation of therapeutically active amides of isoindole, isoquinoline and indole derivatives and succinic acid derivatives |
| KR1019920005274A KR100192530B1 (en) | 1991-03-30 | 1992-03-30 | Succinic acid compounds |
| AT92302786T ATE134615T1 (en) | 1991-03-30 | 1992-03-30 | Succinic acid derivatives |
| ES92302786T ES2084275T3 (en) | 1991-03-30 | 1992-03-30 | SUCCINIC ACID COMPOUNDS. |
| DE69208496T DE69208496T2 (en) | 1991-03-30 | 1992-03-30 | Succinic acid derivatives |
| US07/860,023 US5202335A (en) | 1991-03-30 | 1992-03-30 | Succinic acid compounds |
| EP92302786A EP0507534B1 (en) | 1991-03-30 | 1992-03-30 | Succinic acid compounds |
| HK98104547A HK1005449A1 (en) | 1991-03-30 | 1998-05-27 | Succinic acid compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3142275A JP2686861B2 (en) | 1991-03-30 | 1991-03-30 | Novel benzylidene succinic acid derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH04330055A true JPH04330055A (en) | 1992-11-18 |
| JP2686861B2 JP2686861B2 (en) | 1997-12-08 |
Family
ID=15311571
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3142275A Expired - Fee Related JP2686861B2 (en) | 1991-03-30 | 1991-03-30 | Novel benzylidene succinic acid derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2686861B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998032736A1 (en) * | 1997-01-29 | 1998-07-30 | Kissei Pharmaceutical Co., Ltd. | Process for producing benzylsuccinic acid derivatives |
| JP2007191494A (en) * | 1995-06-20 | 2007-08-02 | Takeda Chem Ind Ltd | Medicine |
-
1991
- 1991-03-30 JP JP3142275A patent/JP2686861B2/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007191494A (en) * | 1995-06-20 | 2007-08-02 | Takeda Chem Ind Ltd | Medicine |
| WO1998032736A1 (en) * | 1997-01-29 | 1998-07-30 | Kissei Pharmaceutical Co., Ltd. | Process for producing benzylsuccinic acid derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2686861B2 (en) | 1997-12-08 |
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